Περίληψη σε άλλη γλώσσα
Beneficial effects of sildenafil on tissue perfusion and proinflammatory molecules expression in a murine model of hind limb ischemia and atherosclerosis.Background: Sildenafil, a phosphodiesterase type 5 antagonist has endothelium protective and angiogenic effects. We tested the hypothesis that sildenafil might improve tissue perfusion and neovascularization and downregulate proinflammatory molecules following limb ischemia.Methods: 30 ApoE-/- male mice,10 weeks old, bred with cholesterol rich diet for 4 weeks, were anesthetized and underwent sunilateral hind-limb ischemia with ligation of the left femoral artery. Mice were randomized in two groups and received sildenafil (1mg/Kg for 7 days in 0.4ml solution, intraperitoneally i.p.), or normal saline (0.4ml for 7days, i.p.). Bilateral hind-limb perfusion was estimated by laser Doppler perfusion imaging after surgery on days 1, 7 and 28. sICAM-1, sVCAM-1, MMP-9, sE-Selectin and tPAI-1 levels were evaluated at days 1 and 28 with enzyme- ...
Beneficial effects of sildenafil on tissue perfusion and proinflammatory molecules expression in a murine model of hind limb ischemia and atherosclerosis.Background: Sildenafil, a phosphodiesterase type 5 antagonist has endothelium protective and angiogenic effects. We tested the hypothesis that sildenafil might improve tissue perfusion and neovascularization and downregulate proinflammatory molecules following limb ischemia.Methods: 30 ApoE-/- male mice,10 weeks old, bred with cholesterol rich diet for 4 weeks, were anesthetized and underwent sunilateral hind-limb ischemia with ligation of the left femoral artery. Mice were randomized in two groups and received sildenafil (1mg/Kg for 7 days in 0.4ml solution, intraperitoneally i.p.), or normal saline (0.4ml for 7days, i.p.). Bilateral hind-limb perfusion was estimated by laser Doppler perfusion imaging after surgery on days 1, 7 and 28. sICAM-1, sVCAM-1, MMP-9, sE-Selectin and tPAI-1 levels were evaluated at days 1 and 28 with enzyme-linked immunosorbent assay (ELISA).Results: Treatment with sildenafil was associated with significantly increased perfusion in the ischemic limb compared to control animals. The increase in blood flow was maintained at day 28. Ischemia exerted no significant effects on sICAΜ-1 (from 1.92± 0.44 ng/ml to 1.41 ± 0.55 ng/ml, p = NS), sVCAM-1 (from 23834 ± 236 MFI units to 23575 ± 425 MFI units, p = NS), MMP-9 (from 1419 ± 1200 MFI units to 701 ± 653 MFI units, p = NS), sE-selectin (from 4.24 ± 2.48 ng/ml to 2.69 ± 2.86 ng/ml, p = NS), and tΡΑΙ-1 (from 0.24 ± 0.16 ng/ml to 0.13 ± 0.16 ng/ml, p = NS). Sildenafil significantly decreased sICAM-1 levels (from 2.14 ± 0.43 ng/ml to 1,23 ± 0,07 ng/ml, p=0.012, p<0.05), sVCAM-1 (from 23894 ± 347 MFI units to 23073 ± 1105 MFI units, p=0.012, p<0.05), sΕ-selectin (from 5 ± 1,40 ng/ml to 2,34 ± 1,29 ng/ml, p=0.012, p<0.05), tΡΑΙ-1 (από 0.14 ± 0,07 ng/ml σε 0,07 ± 0,03 ng/ml, p=0.017, p<0.05), whereas Sildenafil had no significant effects on MMP-9 levels (from 1061 ± 800 MFI units to 544 ± 449 MFI units, p=NS). Conclusions: Sildenafil exerts significant beneficial effects on tissue perfusion and neovascularisation after limb ischemia and downregulates adhesion molecules in the atherosclerotic milieu.
περισσότερα